The adolescent brain is still developing and highly vulnerable to chemical influences. From a neurobiological perspective, children and adolescents are not small adults, and they are more vulnerable to the adverse effects of drugs, chemicals, or diseases. Any chemical impact on a brain that is still developing and pruning neuronal connections can affect this process and alter the course of what should have been the adult destiny of the brain. By virtue of the ongoing developmental processes, adolescent drug exposure can have far more serious consequences than adult drug exposure. In a behavioral and a molecular analysis, we will test the hypothesis that binge-administration of cocaine during adolescence affects the biology and function of the prefrontal cortex (PFC) in adulthood. The PFC is critical for cognitive processing during early development and into adulthood. Dopamine plays an important role in the development of the PFC and of these cognitive abilities. An artificial alteration of dopamine levels by chemicals such as cocaine during adolescence could have a profound effect on cognitive processing in adulthood. In two specific aims we plan to address the potential long-term effect of cocaine exposure during adolescence on (1) a PFC-specific test, the attentional set-shifting task, and (2) on adult gene expression patterns in two areas of the PFC. Both specific aims will be carried out ten days after finishing the cocaine binge-paradigm, and in adulthood three and six weeks after the end of cocaine administration. Molecular analysis will also be carried out during cocaine administration. We expect to see altered PFC function and biology long after cocaine administration has seized. If this paradigm proves to be predictive of adolescent cocaine administration, we will, in future proposals, investigate the consequences of adolescent cocaine administration on other behaviors and brain areas relevant to drug abuse.